TITLE

Promoter Polymorphism of the Anion-Exchange Protein 1 Associated with Severe Malarial Anemia and Fatality

AUTHOR(S)
von Kalckreuth, Vera; Evans, Jennifer A.; Timmann, Christian; Kuhn, Daniela; Agbenyega, Tsiri; Horstmann, Rolf D.; May, Jürgen
PUB. DATE
October 2006
SOURCE
Journal of Infectious Diseases;10/1/2006, Vol. 194 Issue 7, p949
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The anion-exchange protein 1 (AE1 or band 3) is involved in the erythrocyte invasion of the malaria parasite Plasmodium falciparum, the adhesion of infected erythrocytes to endothelial cells, and the regulation of acid-base homeostasis, which is a critical factor for human survival in severe malaria. A variant of the AE1 gene promoter 512 base pairs (bp) distant from the transcription start site and 5699 bp from the translation start codon (AE1-5699T→C) has been shown to be highly frequent in a population from the Ashanti region, Ghana. In a matched-pair case-control study (736 pairs), children heterozygous for the mutation (AE1-5699CT) had an increased risk of severe malarial anemia (odds ratio [OR], 1.45 [95% confidence interval {CI}, 1.05–2.01]; P<.03). In children who developed this complication, carriers of the mutation AE1-5699C had a higher fatality rate than those with the genotype AE1-5699TT (relative risk, 7.1 [95% CI, 1.0–52.8]). Moreover, in children with cerebral malaria, AE1-5699C was positively associated with a distinctive metabolic acidosis (P<.02), and results of luciferase assays showed higher transcriptional activity of the AE1-5699C allele. These results demonstrate that the AE1 promoter allele might influence the infection phenotype and the risk of fatal outcome in children with severe malaria. In this regard, a crucial role of the AE1 protein in malaria is emphasized.
ACCESSION #
22251246

 

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